Effect of nutrition intervention on cognitive development among malnourished preschool children: randomized controlled trial

Childhood malnutrition impairs health, development, and productivity in adulthood. Underweight children have been found to have a variety of cognitive abnormalities. The present study examined the effect of a nutrition-focused intervention on cognitive development among malnourished preschool children between 3 and 5 years of age residing in selected villages of Udupi district, Karnataka. A cluster of 12 villages was chosen randomly. The trial had enrolled preschool children (n = 253) from randomly assigned selected villages to intervention (n = 127) and control arms (n = 126). The mothers in the intervention arm received nutrition-focused intervention and reinforcement of health teaching for 12 months. The post-intervention outcome on the cognitive development of malnourished children was measured at 6 months and 12 months. Statistical analyses indicated that 52% of children in the intervention group had average cognitive development scores on the pre-test, whereas on the post-test, only 5.5% were in the average level of cognitive development. In the control group, the average cognitive development status of the children decreased from 44.4% in the pretest to 26.2% in the post-test. The cognitive development of malnourished children in the intervention group improved compared to the control group (p < 0.001). This study revealed that home-based nutrition-focused food helps to enhance children’s cognitive development. Trial registration: ctri@gov.in. CTRI/31/03/2017/008273 [Registered on: 31/03/2017].

Malnutrition in children is expressly detrimental. The damage to physical and cognitive development during early childhood is largely irretrievable 1 . A wide range of cognitive deficits has been reported in malnourished children 2 . Malnutrition is linked to suboptimal brain development, which has a negative impact on cognitive development, educational achievement, and economic productivity later in life 3 . During childhood, the maturation of specific brain areas is associated with the development of specific cognitive functions, such as language, reading, and memory. Synaptic density reaches a high level of brain growth during childhood age, and brain myelination (which regulates higher cognitive functions) persists well into adolescence 4 .
The genetic program that determines how each person's brain develops is modified by the environment, including nutrition 5 . Studies have demonstrated a link between good nutrition and optimal brain function 6,7 . Healthy nutrition supplementation plays a critical role in cell proliferation, DNA replication, neurotransmitter, and hormone metabolism and is an essential component of enzyme systems throughout the brain 8 . Early in childhood, the brain grows more quickly than the rest of the body, which could make it more susceptible to nutritional deficits 9 .
One of the factors affecting cognitive development is nutrition. Early childhood may be especially vulnerable to nutritional deficiencies due to the rapid brain growth throughout this period. Children who are malnourished have higher mortality and morbidity rates 10 . In preschoolers, impaired cognitive development is predictive of www.nature.com/scientificreports/ later school achievement 11 . Education increases one's human capital or the knowledge, resources, and skills that eventually determine health and well-being 12 . Poor motor and cognitive development, lower educational attainment, economic output, and a higher chance of developing metabolic illnesses can all have an impact on productivity during adulthood, which is a public health concern 13,14 . Studies have reported poor motor skills, adaptive behavior, language, and social skill development among malnourished children. Malnutrition is also linked to deficits in memory, visuomotor coordination, and social skills. Also, decreased IQ scores were associated with the severity of malnutrition 2 . Despite the efforts of national and international obligations, the knowledge gaps of caregivers remain a cause for the nutritional status of children, and it affects physical growth and cognitive development. Considering this, the current study made an effort to give mothers comprehensive nutrition education to increase their understanding of and sensitise them to the prevention and management of malnutrition, change dietary habits, and enhance their children's cognitive development.

Material and methods
Study design and sample. This study employed a cluster-randomised controlled trial design. The cluster of moderate and severe uncomplicated underweight preschool children between three and five years of age attending Anganwadi centers and their mothers in rural areas of Udupi district, Karnataka, were included in the study. Udupi district is a coastal part of Karnataka, India (Fig. 1).
Sample size. The sample size for the study was calculated considering 80% power, 5% level of significance, an attrition rate of 20%, a design effect of 1.5, an improvement of cognitive status in the standard of care of 30%, and 50% improvement in researcher intervention. Considering these, the required sample size was 230 for the intervention and control groups (115 in each group). Thus, 253 samples were included in the study from the selected clusters (127 + 126).
Eligibility criteria for selection of sample. Inclusion criteria. The study included children between 3 and 5 years with moderate and severe underweight registered in Anganwadi centers and their mothers who could read/write/understand Kannada (local language) or English.
Exclusion criteria. Children aged between 3 and 5 years with known cases of systemic illness such as cardiac problems, renal problems etc., and not registered in Anganwadi centers were excluded from the study.
Ethical approval. All  A detailed subject information sheet was given in the local language (Kannada) to all the mothers, and informed consent was obtained from each mother after explaining the purpose of the study and methodology and ensuring the confidentiality of the data obtained.
Assessment of cognitive status. The cognitive status of the children was assessed with a standardized tool, "Cognitive development test for pre-scholars Scale" (PCDTP-p) 15 for Indian children between 3 and 6 years www.nature.com/scientificreports/ of age by verbal and non-verbal tests. Dr Hema Pandey developed the tool to assess the cognitive development of Indian preschoolers. The tool includes six areas such as conceptual skills, information, comprehension, visual perception, memory, and object vocabulary. The tool had high validity, and the author reported test re-test reliability value is r = 0.95. The researcher also checked the current setting's content validity (CVI = 1) and reliability using the test re-test method (r = 1). The assessor administered the test individually in an exclusively private room. Each child was given sufficient time to complete all the test items. Before the test, the child was made physically comfortable. Test results were recorded simultaneously on the scorecards. For each correct answer, one mark was awarded. The total score constituted the 'raw' scores of the subject (child). The total raw scores were converted to standard scores as per their age according to the table of norms and instructions provided along with the tool by the original authors of the tool. The following formula for conversion of raw score to standard score (Z-scores) was used. Z-Score = (X−M/ SD): where X, score; M, mean of the raw score; SD, standard deviation of raw scores.
Based on the z score, the child's cognitive development was interpreted (Table 1).
Randomization and procedure for data collection. Cluster randomization was adopted to select the villages. Twelve villages were chosen randomly for the study. Clusters of six villages were randomly assigned for the intervention, and six villages to the control group using the lottery method by the researcher. All Anganwadi centers belonging to allocated villages were included. Based on anthropometric indices, malnutrition status was identified. All malnourished children who met the inclusion criteria were included in the study. One hundred twenty-seven preschool children and their mothers from 27 Anganwadi centers in six villages were recruited for the intervention group, and 126 preschool children and their mothers from 30 Anganwadi centers in six villages were recruited for the control group (Fig. 2). Data were collected between March 2018 and May 2019. The researcher visited Anganwadi centers, and the weight and height of the children were measured. We evaluated the children's nutritional status using weight-for-age and height-for-age indicators and graded the malnutrition level per NCHS's new WHO child growth standards 16 . Moderate underweight was defined as a weight-for-age ratio of less than − 2 z score, severe underweight was defined as weight for age less than − 3 z score, and stunting was defined as a height-for-age − 2 z score. Moderately and severely underweight preschool children and their parents were selected for the study. The mothers of the malnourished children were met and informed about their children's malnutrition, the purpose of the study, the data collection procedure, intervention, and followups. The date and time for intervention at the Anganwadi center were set. The study's nature was explained in detail, a subject information sheet was distributed in the local language, and informed consent was obtained.
After the mother signed the informed consent, baseline information was collected from the mother, and the researcher assessed the children's cognitive development. With the help of power points, posters, and flipcharts, the mothers were educated on malnutrition, its causes, signs, and symptoms, how to identify malnutrition, the consequences of malnutrition on health and development in a child's life, and a discussion was held on methods to prevent and manage malnutrition at home. A balanced diet, a malnourished child's dietary requirements, and a sample diet menu plan for moderate and severe malnourished preschool children were also discussed.
One of the nutritious recipes, i.e., mixed vegetables and gram (paustic khichdi), was demonstrated. Additionally, the preparation of various healthy recipes rich in protein, energy, calcium, and iron were explained. The module on the Home-based management of malnutrition was given to the mothers, and they were advised to read it well and follow the practices presented in the module. Mothers were asked to prepare anyone nutritious food daily (or at least four times per week) and maintain a diary. They were also asked to send pictures of feeding the child with the recipe and clarify their doubts during the follow-up visit or telephonically. The monthly nutritional level assessment was carried out, and the findings are published 20 .
Follow-up and outcome measurement. Mothers' queries were answered during the intervention phase, and suggestions were given when children had problems. Diary on nutritious diet preparation maintained by the mothers and dietary practices were checked during follow-up.
The outcome assessor performed an outcome assessment of cognitive development. The outcome assessor is a trained, qualified, graduated registered nurse and was blinded by the study group. The outcome measurement of cognitive development assessment was assessed at the end of six months (midline test) and 12 months (endline test) after the intervention in both groups.

Baseline characteristics of enrolled children
The mean age of children in the intervention group was 4.08 ± 0.71, and in the control group, it was 3.95 ± 0.68. A maximum number of children in both groups belonged to the family with a family income of less than 10,000 rupees/per month. The educational status of the parents (both mother and father) was lower in the intervention group than in the control group. Most of the fathers' occupations were reported as self-employed and mothers' occupation were reported as small/self-business in both groups (Table 2). However, the comparison of baseline www.nature.com/scientificreports/ characteristics of both groups showed that, except for parents' educational level, both groups were similar at baseline ( Table 2). Table 3 demonstrates that most of the malnourished children in both groups at baseline had average and aboveaverage cognitive development (intervention and control group). At baseline, 52% of children in the intervention group were classified as having average cognitive development; however, these numbers dropped by 14.2% in the  www.nature.com/scientificreports/ midline test and 5.5% in the endline test and moved to the category of high and extremely high development. At the start of the trial, 44.4% of the children in the control group had average cognitive development; this number dropped to 28.6% at the midline and 26.2% at the endline test. Similarly, compared to the control group, more children in the intervention group scored high in the high and extremely high development categories on the midline and end-line tests ( Table 3). Table 4 shows a significant difference in the baseline and midline test (Mc χ 2 (df) = 78.89 (1) , p = < 0.001); baseline and endline test (Mc χ 2 (df) = 53.94 (1) , p = < 0.001) of cognitive development scores. It is inferred that there was a significant improvement in the cognitive development scores of children in the intervention group over 12 months.

Comparison of pretest and post-test cognitive development status between the intervention and control groups
There was a significant improvement in children's cognitive development from the baseline to the midline test. At six months of intervention (midline), 82 (64.6%) and 72 (57.1%) in both the intervention and the control group, respectively, were in the positive change category of cognitive development. The more positive category was higher (21.3%) in the intervention group than in the control group (12.7%), which was statistically significant (p = 0.006) ( Table 5).
In the intervention group, there was a significant increase in cognitive development from the pretest to the endline test, which was statistically significant (p < 0.001). In the midline and end-line tests, children in the intervention group moved from positive change (21.3%) to more positive change (36%). However, it was noticed that the more positive difference in the control group declined from the midline test (16,12.7%) to the endline test (7, 5.6%). This explains a substantial difference in preschoolers' cognitive development between the intervention and control groups ( Table 6).
Discussion. Various factors, including nutrition, influence the brain development. Nutritional deficiencies may have a significant impact on brain development 9 . In this study, we found that most of the preschoolers with malnutrition had poor cognitive development. We observed that 52% of malnourished preschool children in the intervention group and 44.4% in the control group had average cognitive development. We observed that, except for the motor speed and coordination test, malnourished children performed poorly on tasks requiring attention, working memory, learning and memory, and visuospatial ability. A study found that cognitive skills such as working memory, visual construction, learning, and memory in malnourished children were not developed as per age compared to adequately nourished children 2 , which supports the current study's findings.
In another study, children with malnutrition obtained lower social quotient scores than normal children. The effect was more noticeable in stunted, wasted children with poor communication and socialisation skills. Additionally, malnutrition had a significant relationship with immediate and delayed memory 17 . Higher absenteeism, falling sick, and poor school performance were found among Filipino children 18 .  Table 5. Comparison of pretest and midline test cognitive development status between the intervention and control groups. Note: For the interpretation and understanding, the changes indicated are "neutral" as average cognitive development, above-average cognitive development as "positive change, " high development as "more positive change, " and below-average development as "negative change". www.nature.com/scientificreports/ Significant improvement in the cognitive development of preschool children was observed after implementing community-based nutrition intervention. The intervention developed and delivered was context-specific and affordable to the rural population 19 . Mothers exhibited enthusiasm in preparing varieties of nutritious food that were readily available and affordable to the family. We also observed an improvement in nutritional status among these children 20 . A community-based study from Indonesia reported improvement in the growth and development of children 19 . A systematic review of the effectiveness of early childhood interventions in promoting cognitive development revealed that the implementation of comprehensive programs on cognitive development was very effective. Interventions such as child-focused education and stimulation, parent-focused support, income supplementation, and nutrition and health interventions were effective in improving the cognitive development of children 21 . Food prepared by the mothers promote weight gain and cognitive development because the mothers can find food sources based on local availability, and children prefer local food prepared by the mothers 22 . Nutrition education intervention can improve the child's growth parameters and overall development, including cognitive development. This intervention can be implemented within the integrated child development scheme (ICDS) framework so that mothers can provide nutritious diets to their children within their socioeconomic capabilities.
Strength of the study. The outcome assessor, blinded to the study group, performed an outcome assessment of cognitive development. The outcome measurement, cognitive development, was assessed for a long duration, i.e., at the end of six months and 12 months after the intervention in both groups.
Limitations of the study. The study included only preschool children and their mothers registered in the Anganwadi centres of selected villages of Udupi taluk. The intervention and control groups differed in terms of the parent's educational level. The researcher could not control this as the study adopted cluster randomization.

Conclusion
Malnutrition among children impacts their cognitive development. Thus, caregivers must be made aware of the effect of malnutrition on cognitive development so that they will be able to identify these deficits early and take corrective measures. Parenting and its related feeding practices in the first five years of life are closely related to stimulating children's overall growth and development.

Data availability
The data generated/or analysed during the current study are not publicly available due to confidentiality and ethical concerns. Still, they are available with the first author (Ms Ansuya) and/or corresponding author (Baby S. Nayak) on reasonable request.  Table 6. Comparison of pretest and endline test cognitive development status between the intervention and control groups. For interpretation and understanding, the changes indicated are "neutral" as average cognitive development, above-average cognitive development as "positive change, " high development as "more positive change, " and below-average development as "negative change".